An unprecedented alteration in mode of action of IsCT resulting its translocation into bacterial cytoplasm and inhibition of macromolecular syntheses

Scientific Reports
Jitendra K TripathiJimut Kanti Ghosh

Abstract

IsCT, a 13-residue, non-cell-selective antimicrobial peptide is comprised of mostly hydrophobic residues and lesser cationic residues. Assuming that placement of an additional positive charge in the non-polar face of IsCT could reduce its hydrophobic interaction, resulting in its reduction of cytotoxicity, an analog, I9K-IsCT was designed. Two more analogs, namely, E7K-IsCT and E7K,I9K-IsCT, were designed to investigate the impact of positive charges in the polar face as well as polar and non-polar faces at a time. These amino acid substitutions resulted in a significant enhancement of therapeutic potential of IsCT. IsCT and E7K-IsCT seem to target bacterial membrane for their anti-bacterial activity. However, I9K-IsCT and E7K,I9K-IsCT inhibited nucleic acid and protein syntheses in tested E. coli without perturbing its membrane. This was further supported by the observation that NBD-IsCT localized onto bacterial membrane while NBD-labeled I9K-IsCT and E7K,I9K-IsCT translocated into bacterial cytoplasm. Interestingly, IsCT and E7K-IsCT were significantly helical while I9K-IsCT and E7K,I9K-IsCT were mostly unstructured with no helix content in presence of mammalian and bacterial membrane-mimetic lipid vesicles. Altogether, the r...Continue Reading

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Citations

Feb 28, 2016·Applied Microbiology and Biotechnology·Lifen ZongJianhua Wang
Jun 29, 2017·Antibiotics·Roberto de la Salud BeaQuentin M Buck
Oct 24, 2019·Journal of Peptide Science : an Official Publication of the European Peptide Society·Isabel Cristina Chica AcevedoVani Xavier Oliveira
Jul 26, 2019·Fitoterapia·Alaa SweidanLatifa Bousarghin
Jun 6, 2021·Journal of Colloid and Interface Science·Danubia Batista MartinsMarcia Perez Dos Santos Cabrera

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Methods Mentioned

BETA
circular dichroism
FACS
confocal microscopy
reverse phase analytical chromatography
scanning electron microscopy
ELISA

Software Mentioned

JASCO
CellQuest Pro
Prism
ExPASy
HydroMCalc
SSE ( Secondary Structure Estimation )

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